Heparin-like compounds improve the biophysical properties of eosinophilic mucus

BACKGROUND: In eosinophilic chronic rhinosinusitis (ECRS), eosinophil extracellular traps (EETs) formed via extracellular trap-forming cell death contribute to abnormal mucus properties, including increased viscosity and hydrophobicity, which exacerbate disease progression. This study aimed to determine the modulatory effects of heparin-like compounds on the viscosity, hydrophilicity, and water content of EET-rich mucus in ECRS, and to assess their potential as adjunctive agents in enhancing mucolytic efficacy. METHODS: Mucus samples obtained from six patients with ECRS were treated with heparin-like compounds, including unfractionated heparin, mucopolysaccharide polysulfate (MPS), and dalteparin. Shear viscosity was measured using a rotational viscometer, hydrophobicity was assessed by contact-angle measurements, and water content was determined by thermogravimetric analysis based on time-dependent weight changes and final dry weight. The effects of these compounds on EETs were evaluated using peripheral blood-derived eosinophils in vitro. RESULTS: Treatment with heparin-like compounds, similar to unfractionated heparin, reduced the viscosity of ECRS mucus and EET aggregates while increasing both the water content and hydrophilicity. These compounds also promoted the relaxation of EET structures, and co-treatment with DNase further enhanced mucus dissolution. Increased turbidity upon mixing with histones indicated a direct interaction between heparin-like compounds and histones. CONCLUSIONS: These findings suggest that heparin-like compounds interact with EET-associated histones and alter the mucus polymer network, thereby improving the biophysical properties of pathological mucus by reducing its viscosity and enhancing its hydrophilicity.